The current invention relates to high refractive index, optically clear, silicone polymers, which are used, for example, to make intraocular lenses (IOL).
Optically clear materials, such as glass, polymethylmethacrylate and cured silicone materials, are used in intraocular lenses and are currently known in the art. In order to be useful for such lenses, the materials must have a number of suitable properties including optical clarity, appropriate mechanical properties, relatively low density, resistance to discoloration, and biological compatibility for long-term implantation as a medical device. The refractive power of a lens is a function of its optic shape and the refractive index of the material from which it is made. The higher the refractive index, the thinner a lens can be made for a specified power. Thus, refractive index is a very important property for materials used to make IOL""s.
The flexibility of the materials is important to permit implanting intraocular lenses through small incisions for cataract surgery. Use of a flexible material permits folding or compression of the lens and/or supporting elements, such as haptics, during or prior to insertion, to reduce the size of the incision required. A smaller ocular incision reduces trauma and permits the use of sutureless incision techniques, thus reducing the potential for distorting the shape of the eye and inducing astigmatism.
Aphakic IOLs are used for replacement of the natural lens for treatment of cataracts. Phakic IOLs are used for the correction of myopia and hyperopia where the natural lens is not removed. Posterior chamber phakic lenses have been shown to improve best spectacle corrected visual acuity over external lenses. Most cataract IOLs are implanted in the space created by surgical removal of the diseased natural lens. Posterior chamber phakic IOLs require thinner and more flexible lens construction than the traditional aphakic, cataract IOLs to permit implantation between the iris and the natural lens (that is, in the posterior chamber of the eye) where a thick or stiff lens makes it difficult to avoid disrupting the normal functions of the eye, such as accommodation (focusing) of the natural lens, constriction and dilation of the iris, and the flow of the aqueous fluid (or humor) of the eye. Soft and flexible materials are especially important for phakic IOLs to allow the implant to move with the dynamics of the anatomy. A lens made from a material with high refractive index can be thinner and provide the same refractive power as a thicker lens made from a material having a low refractive index. Thinner lenses are inherently more flexible and are more easily folded or compressed for insertion through small incisions.
Such materials as silica have been used to reinforce optically clear silicones to increase tensile and tear strength. However, silica reinforcement also increases the stiffness of the material which may not be desirable for use in phakic IOLs. Also, reinforcing materials must have the same refractive index as the base material to achieve optical clarity. For example, if a 1.50 refractive index silicone is reinforced with silica which has a refractive index 1.46, the resulting material would scatter light and not be suitable for use as a lens. Thus, the use of reinforcing materials is difficult to execute in a lens, and it would be useful to be able to formulate reliably strong, optically clear silicone materials without using reinforcing agents.
The use of multiple IOLs (xe2x80x9cpiggybackedxe2x80x9d) to achieve a specific optical power is a new technique used by surgeons where the specific required power is not available in a single lens or where a correction in power is required post-operatively. Addition of a lens to a sudophakic eye (where the natural lens has been removed and replaced with an IOL) is another application of the present invention since high refractive index, UV absorbency, and flexibility are important characteristics of such lenses.
Ultraviolet light (UV) absorbing materials are important for ocular prosthetics, such as IOLs, to avoid damage to tissues (such as the retina) from normal exposure to sunlight and other sources of UV light. Further, it is essential that such materials remain optically clear and avoid yellowing or other discoloration resulting from deposits or precipitates within the lens or on its surface. Methods for blocking UV light that are known in the art include the use of benzotriazole in the lens as an additive or as part of a copolymer.
There is, therefore, a need for an intraocular lens made from implantable materials with a high refractive index, that will absorb UV light, and provide adequate mechanical properties including a very high level of flexibility, while avoiding additives and agents that may be extractable or leachable or discolor the lens.
The current invention is useful in aphakic IOLs for the treatment of cataracts. However, the invention is particularly useful in phakic IOLs for refractive surgery. The development of phakic IOLs for the correction of myopia and hyperopia where the natural lens is not removed is described in U.S. Pat. No. 4,585,456, Blackmore, issued Apr. 29, 1986. The use of phakic IOLs has been shown to improve best spectacle corrected visual acuity (Dimitrity Dementiev M. D. and Alexander Hatsis, M. D., Symposium on Cataract, IOL and Refractive Surgery, Session 3-B, Apr. 26-30 1997, Boston Mass., ASCRS, Fairfax, Va.). Posterior chamber phakic IOLs require thinner and more flexible lens construction than the traditional aphakic IOLs for the treatment of cataracts where the IOL is implanted in the space created by the surgical removal of the natural lens.
Optically clear silicone materials with a relatively high refractive index are known in the art. Such materials are typically formulated by the use of additives or co-monomers in the silicone polymer material; this generally results in undesirable trade-offs in the other properties of the material, such as strength, flexibility, elasticity or elongation.
Canadian Patent 1,273,144, Nishimura, published Aug. 21, 1990, discloses the inclusion of refractive index-modifying groups, such as phenyl groups, into hydride-containing siloxanes by reacting a portion of the hydride groups with carbon- carbon unsaturated bonds in the refractive index-modifying group. After this reaction, the unreacted hydride groups in the modified hydride-containing siloxane are reacted with a compound having at least two carbon-carbon unsaturated bonds to form a cross-linked polysiloxane. This system is somewhat difficult to control and may not be suited for mass production of silicone lenses because of potentially large batch-to-batch quality variations. For example, the refractive index-modifying groups must be sufficiently numerous and evenly distributed in the hydride-containing siloxane to provide for the desired refractive index without detrimentally affecting the other properties of the final polymer. At the same time, the unreacted hydride groups remaining in the siloxane must be sufficiently numerous and evenly distributed to provide for the desired cross-linking reaction. These factors can create a reaction control problem which may result in the final polymer not having the desired refractive index and /or not having one or more other desired physical properties.
U.S. Pat. No. 4,882,398, Mbah, issued Nov. 21, 1989, discloses optically-clear silicone compounds adaptable for use in windows, windshields and lenses. Although this patent does disclose certain aryl and aralkyl groups attached or bonded to a siloxane , there is no teaching or suggestion of the effect of such substitution on the refractive index of the final polymer. Also, the amount of these groups which is included should have little or no effect on the refractive index of the final polymer and would yield a low refractive index of about 1.41. This is consistent with the fact that for many of the disclosed uses (e.g., windows, windshields), refractive index is not a critical property.
Gas permeable, wettable and hydrophilic materials are well-known in the art for use in contact lenses and other applications. Examples of such materials are disclosed in U.S. Pat. Nos. 4,099,859, Merrill, issued Jul. 11, 1978; U.S. Pat. No. 4,120,570, Gaylord, issued Oct. 17, 1978; U.S. Pat. No. 4,139,513, Tanaka, issued Mar. 20, 1978; U.S. Pat. No. 4,139,523, Tanaka, et al., issued Feb. 13, 1979; U.S. Pat. No. 4,139,692, Tanaka et al., issued Feb. 13, 1979; U.S. Pat. No. 4,261,875, Le Boeuf, issued Apr. 18, 1981; U.S. Pat. No. 4,277,595, Deichert et al., issued Jul. 7, 1981; U.S. Pat. No. 4,410,674, Ivani, issued Oct. 18, 1983; U.S. Pat. No. 4,447,981, Arkles, issued Oct. 23, 1984; U.S. Pat. No. 4,507,452, Foley; issued Mar. 26, 1985; U.S. Pat. No. 4,450,264, Choyce, issued May 22, 1982; U.S. Pat. No. 4,463,149, Ellis, issued Jul. 31, 1984; U.S. Pat. No. 4,550,139, Arkels, issued Oct. 29, 1985; U.S. Pat. No. 4,525,563 Shibata et al., issued Jun. 25, 1985; U.S. Pat. No. 4,600,751, Lee et al., issued July 15, 1986; U.S. Pat. No. 4,611,039, Powell et al., issued Sep. 9, 1986; U.S. Pat. No. 5,070,169, Robertson, et al., issued Dec. 3, 1991; U.S. Pat. No. 5,070,170, Robertson et al., issued Dec. 3, 1991; U.S. Pat. No. 5,321,108, Kunzler et al., issued Jun. 14, 1984; U.S. Pat. No. 5,352,714, Lai et al., issued Oct. 4, 1994; U.S. Pat. No. 5,480,946, Mueller, et al., issued Jan. 2, 1996; U.S. Pat. No. 5,346,507, Fedorov et al., issued Sep. 13, 1994; U.S. Pat. No. 5,286,829, Fedorov et al., issued Feb. 15, 1994; and in British Patent 1,480,880, issued Jul. 27, 1977. A hydrophilic material is not desirable for a permanently implanted prosthetic device, such as an IOL, where it is necessary to avoid the eventual discoloration from precipitates that can enter and form deposits within the material or on the surface of the lens.
Inhibitors are used in many silicones to facilitate the manufacturing process by enabling storage of premixed components prior to the polymerization. U.S. Pat. No. 3,436,366, Modic, issued Apr. 1, 1969, discloses filled silicone compositions that do not use an inhibitor but must be stored at 0xc2x0 C. Such storage requirements complicate the manufacture of the material. U.S. Pat. No. 3,188,299, Chalk, issued Jun. 8, 1965, and U.S. Pat. No. 3,188,300, Chalk, issued Jun. 8, 1965, disclose the preparation of silicones in the presence of nitrogen-containing or phosphorous-containing ligands for reducing the activity of a platinum catalyst. U.S. Pat. No. 3,192,181, Moore, issued Jun. 29, 1965, describes an optically clear silicone proposed for use in contact lenses and containing volatile inhibitors to permit storage in sealed containers. In U.S. Pat. No. 3,383,356, Nelson, issued May 14, 1968, it is taught that volatile halocarbon catalyst inhibitor additives can be used in reactive organosilicone compositions for inhibiting polymerzation. U.S. Pat. No. 3,453,233, Flatt, issued Jul. 1, 1969, discloses a mixture of inhibitor and crosslinker compounds. U.S. Pat. No. 4,801,642, Janik, issued Jan. 31, 1989, discloses contact lenses containing hydrophilic silicone polymers with inhibitors containing amines to permit long-term storage. U.S. Pat. No. 5,077,335, Schwabe et al., issued Dec. 31, 1991, discloses an optically-clear silicone which contains inhibitors. Inhibitors taught in the art may be convenient to use in the manufacturing process, but can result in materials which are less biocompatable than non-inhibited compositions because the inhibiting compound may be extractable or add to the potential for release of free radicals from the polymerized composition.
One group of materials known in the art that does not use inhibitors is low temperature vulcanizing (LTV), in situ curing silicones that are injected into the empty capsule of the eye following extraction of the natural lens. Examples of these materials and lenses made from them are disclosed in U.S. Pat. Nos.: 4,122, 246, Sierawski, issued Oct. 24, 1978; U.S. Pat. No. 4,542,542, Wright et al., issued Sep. 24, 1985; U.S. Pat. No. 4,608,050, Wright et al., issued Aug. 26, 1986; U.S. Pat. No. 4,537,943, Talcott, issued Aug. 27, 1985; U.S. Pat. No. 5,391,590, Gerace, issued Feb. 21, 1995; and U.S. Pat. No. 5,411,553, Gerace, issued May 2, 1995 issued. These materials are specifically designed to vulcanize at body temperature and avoid the use of inhibitors by being mixed just prior to use.
Optically clear silicone polymers reinforced by adding silica to improve mechanical properties are well known in the art. Silica reinforced materials are disclosed in the following U.S. Pat. No.: 3,341,490, Burdick, issued Sep. 12, 1967; U.S. Pat. No. 3,383,356, Nelson, et al., issued May 14, 1968; U.S. Pat. No. 3,457,214, Modic, issued Jul. 22, 1969; U.S. Pat. No. 3,996,187, Modic, issued Dec. 7, 1976; U.S. Pat. No. 3,996,189, Modic, issued Dec. 7, 1976; U.S. Pat. No. 4,418,165, Travnicek , issued Nov. 11, 1983; U.S. Pat. No. 4,615,702, Polmanteer et al.; issued Oct. 7, 1986; U.S. Pat. No. 4,785,047, Koziol, issued Nov. 15, 1988; U.S. Pat. No. 4,882,398, Mbah, issued Nov. 21, 1989; U.S. Pat. No. 5,236,970, Christ, issued Aug. 17, 1993; U.S. Pat. No. 5,444,106 Zhou, issued Aug. 22, 1995; U.S. Pat. No. 5,494,946, Christ, issued May 30, 1995; and European Application 110537, Ulman, et al. published Jun. 13, 1984. These compositions have the advantage of higher resilience, tear and tensile strength, but they also have the disadvantage of greater stiffness due to reinforcement by the silica. Reinforcing with silica also limits the potential for increasing the refractive index beyond 1.46 (the refractive index of silica). If the refractive index of the polymer and the reinforcing material are different, the interface between the two materials will cause light scattering and the final product will appear milky. Therefore, high refractive index materials for IOLs are preferrably made without reinforcing materials, such as silica.
The materials of the present invention and the IOLs made from those materials, are unique in that they:
1. are optically clear and flexible with a refractive index of about 1.50 or greater;
2. have adequate tear and tensile strength that will permit compression for insertion through a small incision or for folding prior to insertion;
3. have adequate resilience for the IOL to return to its original shape following insertion; and
4. have sufficient flexibility to cope with the dynamic movement of the surrounding anatomy after implantation or to permit surgical removal of the device through a small incision at a later date.
In addition, the materials do not discolor, do not require the use of silica reinforcing materials, are biocompatible, and, very unexpectedly, are UV light absorbing.
Ultraviolet (UV) light (wavelength from about 200 to 400 nanometers) absorbing materials are important for ocular prosthetics, such as IOLs, to avoid damage to tissues, such as the retina, from normal exposure to sunlight and other sources of UV. It has become standard practice to add UV stabilizers to light sensitive polymers and to add UV absorbing compounds to corrective lenses (such as eye glasses or IOLs). UV-B rays, in the wave length range of 280 to 320 nanometers, are the most damaging. Means for achieving UV absorbing materials are known in the art. U.S. Pat. No. 3,213,058, Boyle, issued Oct. 19, 1965, discloses a class of optically clear, ultraviolet (UV) light absorbing, vulcanized silicone compositions for use in implantable, medical prosthetic devices, such as intraocular lenses. UV absorbing compounds are incorporated in the material via reaction with carboxy and hydroxy groups contained in silicone compounds. U.S. Pat. No. 4,304,895 (Re33,477), Loshaek, issued Dec. 8, 1981, discloses copolymers for use in hard contact lenses containing benzophenone derivatives that are in steady state with respect to extraction from the lens in an aqueous medium. More specifically, Loshaek discloses the use of 2-hydroxy-4-methacryloxybenzophenone and mixtures thereof as an ultraviolet light absorber that is copolymerizable with acrylic monomers to yield hard contact lenses materials. U.S. Pat. No. 4,310,650, Gupta et al., issued Jan. 12, 1982, discloses copolymerization of an allyl-2-hydroxy-benzophenone with an acrylic ester, such as polymethylmethacrylate for absorbing UV. U.S. Pat. No. 4,528,311, Beard et al., issued Jul. 9, 1985, discloses certain benzotriazole monomers which are copolymerizable with vinyl monomers, such as polymethylmethacrylate, to yield UV absorbing optically clear polymers. U.S. Pat. No. 4,612,358 Besecke et al., issued Sep. 16, 1986, discloses alkyl groups and cyclic groups in compounds susceptible to free-radical polymerization for absorbing UV light. U.S. Pat. No. 4,868,251, Reich, issued Sep. 19, 1989, and U.S. Pat. No. 5,164,462, Yang, issued Nov. 17, 1992, teach the use of alkoxy radicals and halogen groups with a terminal double bond or alkyl radicals to achieve UV absorbency. In U.S. Pat. No. 4,803,254, Dunks, issued Feb. 7, 1989, are taught UV absorbing compositions containing benzotriazole, as well as the use of vinylsilylalkoxy arylbenzotriazole to yield additives that absorb over 90% of the UV light. The compounds are said to be compatible with silicone polymers and can be incorporated into silicone polymers through covalent bonding to impart the UV absorbing properties. Dunks discloses that his materials have a low level of extractables which he achieves by maximizing bonding with the base polymer. U.S. Pat. No. 5,346,507, Fedorov, issued Sep. 13, 1994, discloses UV absorbing compounds for PMMA that are not used for silicones. U.S. Pat. No. 5,376,737, Yang, issued Dec. 27, 1994, discloses a method for introducing a UV absorbing material into a vulcanized solid material such that it is cross-linked or reacted with the improved material and the UV absorbing material cannot be extracted. U.S. Pat. No. 5,444,106, Zhou, issued Aug. 22, 1995, discloses high refractive index silicone compositions for IOLs containing a silica filler and a combination UV absorber and cross-linking reagent. Typically, phenyl chromophores (as used in the present invention) do not absorb light with a wavelength above 300 nm and, therefore, are not known as UV absorbers.
U.S. Pat. No. 4,647,282, Fedorov, et al., issued Mar. 3,1987, discloses materials and methods used to manufacture optical prosthetic devices by polymerization of a mixture of:
A: xcex1,xcfx89-bis-trivinylsilyloligodimethyl(methylphenyl)-siloxane, and
B: xcex1,xcfx89-bis-methyldimethylhydrosiloxyoligomethyl(phenyl)methylhydro-siloxane,
in the presence of a platinum polyaddition reaction catalyst where the ratio of A:B in said mixture is from 100:1 to 100:20 parts by weight. The resulting vulcanized material contains about 12 to 18% phenyl groups and has a refractive index up to 1.48. These non-reinforced materials were successfully biocompatibility and toxicity tested, and IOLs made from these materials were successfully implanted in hundreds of patients (A. V. Tereschenko et al., Ocular Surgery News, 1996, and Dimitrity Dementiev, M. D. and Alexander Hatsis, M. D.; Symposium on Cataract, IOL and Refractive Surgery, Session 3-B, Apr. 26-30 1997, Boston, Mass., ASCRS, Fairfax, Va.). The patent teaches that if the ratio of the A:B mixture is less than about 100:1, the strength of the material is reduced so that it cannot be implanted in the eye without deformation. Also, if said ratio is greater than 100:20, the stiffness achieved is such that a lens made from such material is difficult to insert. Ultraviolet (UV) light transmission for the disclosed materials is 85% to 95%.
U.S. Pat. No. 5,512,609, Yang, issued Apr. 30, 1996, describes high refractive index, siloxane-based, cross-linked polymers which are useful in producing foldable intraocular lenses. The patent teaches that the aryl-containing siloxanes preferably comprise at least about 20% or more of the total silicone-bound substituents.
The prior art does not fully satisfy the need for a very flexible intraocular lens having UV absorbency, excellent biocompatibility, and high refractive index to permit a sufficiently thin lens for some aphakic, sudophakic, and phakic applications. It is, therefore, an object of the present invention to provide IOLs which are optically clear, have a high refractive index (at least about 1.50) to provide thinner lenses with reduced mass, that are UV absorbing, have adequate mechanical properties to withstand folding or compression for insertion through a small incision, have high elasticity and are biocompatible without the use of UV absorbers (such as benzotriazole), reinforcing materials, fillers, or inhibitors.
The present invention is an intraocular lens made from a class of optically clear, ultraviolet (UV) light absorbing, vulcanized silicone compositions having a content of phenyl groups (as used herein, the term xe2x80x9cphenylxe2x80x9d is intended to encompass both unsubstituted and substituted (which are technically xe2x80x9carylxe2x80x9d) groups) of at least about 35 mole % (and preferably at least about 45 mole %), suitable for implanting in the human eye, particularly for use as a phakic lens located in the posterior chamber of the eye. The high mole percentage of phenyl groups in the vulcanized silicone compositions (the vulcanizate) provides a high refractive index (at least about 1.50) and blocks ultraviolet light which can damage the natural lens or the retina. The silicone compositions comprise a polymerized mixture of three polyorganovinyl-siloxane components:
Component I: xcex1, xcfx89-bis(trivinylsiloxy) oligodimethyldiphenylvinylmethylsiloxane;
Component II: xcex1, xcfx89-bis(trimethylsiloxy) oligodimethyldiphenylmethylhydrosiloxane; and
Component III: xcex1, xcfx89-bis(trimethylsiloxy)oligomethylphenylvinylmethylphenyl-siloxane;
which are combined together with
Component IV: a complex polyaddition catalyst (preferably a compound of platinum and hexavinyldisiloxane).
In these silicone component mixtures, the ratio of the four components (I:II:III:IV respectively) ranges from about 0.9:0.1:0.015:0.006 to about 0.7:0.3:0.05:0.01 parts by weight (i.e., Component I may vary from about 0.7 to 0.9 weight parts; Component II from about 0.1 to about 0.3 weight parts; Component III from about 0.015 to about 0.05 weight parts; and Component IV from about 0.006 to about 0.01 weight parts).